1. Field of the Invention
9-(Z)-Retinoic acid is a substance of physiological importance (cf. Nature 355 (1992) 359-361). It has a high binding affinity for the nuclear retinoic acid acceptor RXR.sub..alpha. which is also activated by direct ligand interaction. This interaction has been observed to result in altered gene expression, which makes it possible substantially to influence cellular processes.
Since no utilizable process for the preparation of 9-(Z)-retinoic acid is known to date, it was an object of the invention to develop an advantageous process for its preparation.
2. Description of the Art
The retinoic acid isomer which has been used most commonly to date, all-(E)-retinoic acid, is advantageously prepared by Wittig reaction of a .beta.-ionylideneethyltriphenylphosphonium salt (C.sub.15 -triphenylphosphonium salt) with a .beta.-formylcrotonic ester. Subsequent separation of the resulting double-bond isomers is possible only with extremely elaborate preparative chromatographic methods.
In the preparation of the C.sub.15 -triphenylphosphonium salt required for industrial vitamin A syntheses and for preparing other vitamin A derivatives, such as retinal and retinoic acid, (see, for example, H. Pommer et al. in Angew. Chem. 77 (1965) 277-360) the mother liquor after removal of the required product contains, besides all-(E)-C.sub.15 -triphenylphosphonium salt, the 9-(Z) isomer in a content of 10-60%, in particular 30-55%, of the total weight of C.sub.15 -triphenylphosphonium salt. Direct use of this mother liquor for preparing 9-(Z)-retinoic acid is possible only with great difficulty.